Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease

Background. Celiac disease (CD) is an autoimmune disease that develops in patients with a genetic predisposition, incurring a susceptibility to gluten-containing foods such as barley, wheat, and rye. The elimination of gluten from the diet is the main therapeutic approach and usually leads to clinical and laboratory improvement. There are no ideal markers that objectively assess dietary compliance in CD patients. Materials and methods. Sixty newly diagnosed CD patients (male/female: 43/17) and 40 healthy subjects (male/female: 23/17) were enrolled in this study. The diagnosis of CD was established by both histological findings of duodenum biopsy (total villous atrophy and lymphocytic infiltration) and positive antibodies against endomysium or gliadin. Results. A significantly higher mean platelet volume (MPV) was observed in the CD group compared with healthy subjects (8.45 +/- 0.96 fL versus 7.93 +/- 0.63 fL; p = 0.004). After introduction of a gluten-free diet, the MPV of CD patients in the dietary adherent group was significantly lower than that of the non-adherent group (8.09 +/- 0.6 fL versus 8.9 +/- 1.08 fL; p = 0.001). Overall dietary adherence rate was 71.6% (43/60 CD patients). In the dietary compliant group, initiation of gluten-free diet was associated with a significant decrease in MPV from base-line values (8.56 fL versus 8.25 fL; p = 0.008). In the non-adherent group, MPV on 3-month follow-up was higher than at base-line (8.05 fL versus 8.91 fL; p = 0.001). Conclusion. MPV could be a promising and easily available biomarker for monitoring of dietary adherence in CD patients at a low cost in comparison with other modalities.WoSScopu

Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis

Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC. Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF

High discontinuation rate of azathioprine in autoimmune hepatitis, independent of time of treatment initiation

Contains fulltext : 225262.pdf (Publisher’s version ) (Open Access)BACKGROUND: Guidelines regarding treatment for autoimmune hepatitis (AIH) favour two strategies for azathioprine (AZA) introduction: concurrent with steroids at induction or delayed by 2-4 weeks. The safety and efficacy of both strategies have been unexplored. METHODS: We established a cohort of 900 AIH patients from 12 centres in 7 European countries. There were 631 patients who used AZA as part of the therapeutic regimen. We distinguished two groups: patients with early AZA (<2 weeks) or delayed AZA initiation (≥2 weeks). Primary outcome was discontinuation of AZA in the first year of treatment. Cox regression and propensity score matching was performed to determine difference in outcomes between groups. RESULTS: Patients with early AZA initiation had significantly lower transaminases and bilirubin at baseline. Discontinuation rates of AZA did not differ between early and delayed starters (16.6% vs 14.2%), which did not reach statistical significance (hazard ratio 0.97, 95% confidence interval 0.61-1.55, P = .90). Stratification according to baseline disease activity or propensity score matching did not alter the results. Main reason for AZA discontinuation was intolerance to treatment (14.0% vs 13.2%, P = .78) with nausea and vomiting as main side effects. AIH remission rates were comparable among groups. CONCLUSION: The discontinuation rate of AZA in AIH treatment is ~15% in the first year of treatment. Early or delayed AZA initiation does not differ in remission and discontinuation rates in AIH induction therapy. Our data suggest that either strategy may be used as part of AIH treatment

Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study

Background and Aims: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. Approach and Results: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score?matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. Conclusions: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.Fil: Efe, Cumali. Harran University Hospital; TurquíaFil: Dhanasekaran, Renumathy. University of Stanford; Estados UnidosFil: Lammert, Craig. University School of Medicine; Estados UnidosFil: Ebik, Berat. Gazi Yaşargil Education and Research Hospital; TurquíaFil: Higuera de la Tijera, Fatima. Hospital General de México; MéxicoFil: Aloman, Costica. Rush University Medical Center; Estados UnidosFil: Rıza Calışkan, Ali. Adıyaman University; TurquíaFil: Peralta, Mirta. Latin American Liver Research Educational And Awareness Network; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gerussi, Alessio. University of Milano Bicocca; Italia. San Gerardo Hospital; ItaliaFil: Massoumi, Hatef. Montefiore Medical Center; Estados UnidosFil: Catana, Andreea M.. Harvard Medical School; Estados UnidosFil: Torgutalp, Murat. Universitätsmedizin Berlin; AlemaniaFil: Purnak, Tugrul. McGovern Medical School; Estados UnidosFil: Rigamonti, Cristina. Azienda Ospedaliera Maggiore Della Carita Di Novara; Italia. Università del Piemonte Orientale; ItaliaFil: Gomez Aldana, Andres Jose. Universidad de los Andes; ColombiaFil: Khakoo, Nidah. University of Miami; Estados UnidosFil: Kacmaz, Hüseyin. Adıyaman University; TurquíaFil: Nazal, Leyla. Clínica Las Condes; ChileFil: Frager, Shalom. Montefiore Medical Center; Estados UnidosFil: Demir, Nurhan. Haseki Training and Research Hospita; TurquíaFil: Irak, Kader. SBU Kanuni Sultan Süleyman Training and Research Hospital; TurquíaFil: Ellik, Zeynep Melekoğlu. Ankara University Medical Faculty; TurquíaFil: Balaban, Yasemin. Hacettepe University; TurquíaFil: Atay, Kadri. Mardin State Hospital; TurquíaFil: Eren, Fatih. Ordu State Hospital; TurquíaFil: Cristoferi, Laura. University of Milano Bicocca; Italia. San Gerardo Hospital; ItaliaFil: Batibay, Ersin. Harran University Hospital; TurquíaFil: Urzua, Álvaro. Universidad de Chile. Facultad de Medicina.; ChileFil: Snijders, Romee. Radboud University Medical Center; Países BajosFil: Ridruejo, Ezequiel. Latin American Liver Research Educational and Awareness Network; Argentina. Cerrahpaşa School of Medicine; Turquía. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). Patients and methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.Fil: Efe, Cumali. Harran University Hospita; TurquíaFil: Lammert, Craig. University School of Medicine Indianapolis; Estados UnidosFil: Taşçılar, Koray. Universitat Erlangen-Nuremberg; AlemaniaFil: Dhanasekaran, Renumathy. University of Stanford; Estados UnidosFil: Ebik, Berat. Gazi Yasargil Education And Research Hospital; TurquíaFil: Higuera de la Tijera, Fatima. Hospital General de México; MéxicoFil: Calışkan, Ali R.. No especifíca;Fil: Peralta, Mirta. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Gerussi, Alessio. Università degli Studi di Milano; ItaliaFil: Massoumi, Hatef. No especifíca;Fil: Catana, Andreea M.. Harvard Medical School; Estados UnidosFil: Purnak, Tugrul. University of Texas; Estados UnidosFil: Rigamonti, Cristina. Università del Piemonte Orientale ; ItaliaFil: Aldana, Andres J. G.. Fundacion Santa Fe de Bogota; ColombiaFil: Khakoo, Nidah. Miami University; Estados UnidosFil: Nazal, Leyla. Clinica Las Condes; ChileFil: Frager, Shalom. Montefiore Medical Center; Estados UnidosFil: Demir, Nurhan. Haseki Training And Research Hospital; TurquíaFil: Irak, Kader. Kanuni Sultan Suleyman Training And Research Hospital; TurquíaFil: Melekoğlu Ellik, Zeynep. Ankara University Medical Faculty; TurquíaFil: Kacmaz, Hüseyin. Adıyaman University; TurquíaFil: Balaban, Yasemin. Hacettepe University; TurquíaFil: Atay, Kadri. No especifíca;Fil: Eren, Fatih. No especifíca;Fil: Alvares da-Silva, Mario R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Cristoferi, Laura. Università degli Studi di Milano; ItaliaFil: Urzua, Álvaro. Universidad de Chile; ChileFil: Eşkazan, Tuğçe. Cerrahpaşa School of Medicine; TurquíaFil: Magro, Bianca. No especifíca;Fil: Snijders, Romee. No especifíca;Fil: Barutçu, Sezgin. No especifíca;Fil: Lytvyak, Ellina. University of Alberta; CanadáFil: Zazueta, Godolfino M.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Demirezer Bolat, Aylin. Ankara City Hospital; TurquíaFil: Aydın, Mesut. Van Yuzuncu Yil University; TurquíaFil: Amorós Martín, Alexandra Noemí. No especifíca;Fil: De Martin, Eleonora. No especifíca;Fil: Ekin, Nazım. No especifíca;Fil: Yıldırım, Sümeyra. No especifíca;Fil: Yavuz, Ahmet. No especifíca;Fil: Bıyık, Murat. Necmettin Erbakan University; TurquíaFil: Narro, Graciela C.. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Bıyık, Murat. Uludag University; TurquíaFil: Kıyıcı, Murat. No especifíca;Fil: Kahramanoğlu Aksoy, Evrim. No especifíca;Fil: Vincent, Maria. No especifíca;Fil: Carr, Rotonya M.. University of Pennsylvania; Estados UnidosFil: Günşar, Fulya. No especifíca;Fil: Reyes, Eira C.. Hepatology Unit. Hospital Militar Central de México; MéxicoFil: Harputluoğlu, Murat. Inönü University School of Medicine; TurquíaFil: Aloman, Costica. Rush University Medical Center; Estados UnidosFil: Gatselis, Nikolaos K.. University Hospital Of Larissa; GreciaFil: Üstündağ, Yücel. No especifíca;Fil: Brahm, Javier. Clinica Las Condes; ChileFil: Vargas, Nataly C. E.. Hospital Nacional Almanzor Aguinaga Asenjo; PerúFil: Güzelbulut, Fatih. No especifíca;Fil: Garcia, Sandro R.. Hospital Iv Víctor Lazarte Echegaray; PerúFil: Aguirre, Jonathan. Hospital Angeles del Pedregal; MéxicoFil: Anders, Margarita. Hospital Alemán; ArgentinaFil: Ratusnu, Natalia. Hospital Regional de Ushuaia; ArgentinaFil: Hatemi, Ibrahim. No especifíca;Fil: Mendizabal, Manuel. Universidad Austral; ArgentinaFil: Floreani, Annarosa. Università di Padova; ItaliaFil: Fagiuoli, Stefano. No especifíca;Fil: Silva, Marcelo. Universidad Austral; ArgentinaFil: Idilman, Ramazan. No especifíca;Fil: Satapathy, Sanjaya K.. No especifíca;Fil: Silveira, Marina. University of Yale. School of Medicine; Estados UnidosFil: Drenth, Joost P. H.. No especifíca;Fil: Dalekos, George N.. No especifíca;Fil: N.Assis, David. University of Yale. School of Medicine; Estados UnidosFil: Björnsson, Einar. No especifíca;Fil: Boyer, James L.. University of Yale. School of Medicine; Estados UnidosFil: Yoshida, Eric M.. University of British Columbia; CanadáFil: Invernizzi, Pietro. Università degli Studi di Milano; ItaliaFil: Levy, Cynthia. University of Miami; Estados UnidosFil: Montano Loza, Aldo J.. University of Alberta; CanadáFil: Schiano, Thomas D.. No especifíca;Fil: Ridruejo, Ezequiel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Wahlin, Staffan. No especifíca

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Codoni G, Kirchner T, Engel B, Villamil AM, Efe C, Stättermayer AF, Weltzsch JP, Sebode M, Bernsmeier C, Lleo A, Gevers TJ, Kupčinskas L, Castiella A, Pinazo J, De Martin E, Bobis I, Sandahl TD, Pedica F, Invernizzi F, Del Poggio P, Bruns T, Kolev M, Semmo N, Bessone F, Giguet B, Poggi G, Ueno M, Jang H, Elpek GÖ, Soylu NK, Cerny A, Wedemeyer H, Vergani D, Mieli-Vergani G, Lucena MI, Andrade RJ, Zen Y, Taubert R, Beretta-Piccoli BT, Histological and serological features of acute liver injury after SARS-CoV-2 vaccination, JHEP Reports (2022), doi: https://doi.org/10.1016/j.jhepr.2022.100605.Liver injury with autoimmune features after vaccination against Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of patients with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features

Otoimmün Hepatitte Serum Vitamin-D Düzeyi ve Karaciğer Histolojisi ile İlişkisinin Araştırılması

This study evaluated the Vitamin D levels (Vit-D) of the serum samples which were obtained from patients diagnosed with autoimmune hepatitis (AIH) between November 2010 and September 2013, at the Hacettepe University Department of Gastroenterology. The patients data were obtained from the hospital electronic medical record system (Neksus). A total of 72 subjects, including 43 patients with AIH diagnoses and 29 control group subjects were included in the study. There was no statistically significant difference in the mean age and gender between groups. The mean Vit-D levels in AIH patients were significantly lower than the control group (16.5± 9.9 v.s. 29.3±15.6, p=0.0001). When Vit-D levels <30 was taken as deficiency, Vit-D levels in AIH patients was once more found to be significantly lower when compared to the control group (%86 v.s. %52, p=0.002). When AIH patients were grouped with respect to having early or late stage fibrosis, there were no statistically significant differences in age, gender and biochemical parameters. However, mean Vit-D levels were significantly lower in patients with high fibrosis score, when compared to patients with low fibrosis score (21.8 ± 10.3 v.s 11.0± 5.8, p=0.001). Also, when Vit-D levels <30 was taken as deficiency, patients with advanced stage fibrosis were found to have lower levels when compared to patients with early stage fibrosis (%100 v.s %73, p=0.01). In conclusion, Vit-D levels are significantly lower in patients with AIH. Furthermore, in these patients, there is a negative correlation between Vit-D levels and histological stage.Bu çalışma Kasım 2010-Eylül 2013 tarihleri arasında Hacettepe Üniversitesi, Gastroenteroloji bölümüne başvurup tanı alan otoimmün hepatitli (OİH) hastaların, ilk tanı konulduğu zaman toplanan serumlarında Vitamin-D (Vit-D) düzeyleri değerlendirilerek yapıldı. Hasta bilgileri; hasta dosyaları ve hastane online veri sistemi (Neksus) kullanılarak elde edilmiştir. OİH li 43 vaka ve 29 sağlıklı gönüllüden oluşan kontrol grubu olmak üzere toplam 72 kişi çalışmaya dahil edilmiştir. İki grup arasında yaş ve cinsiyet durumu açısından anlamlı bir fark bulunmadı. Ortalama serum Vit-D düzeyi OİH hastalarında, kontrol grubuna göre anlamlı oranda düşük saptandı (16.5± 9.9 ng/mL karşı 29.3±15.6 ng/mL, p=0.0001). Vitamin D <30 ng/mL olan hastalar ele alındığında ise; bu değerin altında olan OİH li hastaların oranı kontrol grubuna göre anlamlı şekilde yüksekti (%86 karşı %52, p=0.002). OİH hastaları erken ve ileri evre fibrosis açısından değerlendirildiğinde ise, hastalar yaş, cinsiyet ve serum biokimyasal parametreler bakımından benzer özelliklere sahiplerdi. Fakat ortalama Vit-D düzeyi fibrosis skoru yüksek olan hastalarda fibrosis skoru düşük olan hastalara oranla belirgin ölçüde düşük saptandı (21.8 ± 10.3 ng/mL karşı 11.0± 5.8 ng/mL, p=0.001). Vitamin D <30 ng/mL olan hastalar ele alındığında ise, fibrozis evresi ileri OİH hastalarında bu değerde Vit-D düzeyi fibrozis evresi düşük olan gruba oranla anlamlı derecede farklıydı (%100 karşı %73, p=0.01). Sonuç olarak, OİH hastalarda serum Vit-D düzeyi sağlıklı bireylere göre anlamlı biçimde düşük izlenmektedir ve bu hastalarda serum Vit-D düzeyi ile histolojik evre arasında negatif korelasyon söz konusudur